PHARM:(edited) try this drug, write about it, and get thousands of web hits (fwd)

Eugene Leitl (
Fri, 13 Mar 1998 15:44:00 +0300 (MSK)

---------- Forwarded message ----------
Date: Fri, 13 Mar 1998 00:42:56 -0500
From: Treon Verdery <>
Subject: try this drug, write about it, and get thousands of web hits

Someone (Zev Bryant) left a copy of nature:structural biology on my
floor. The article with the heavy reading was related to a new-to-the-west
nootropic herb called huperzia serrata; drug compound in medline as
huperzine. (chinese/sawtooth club moss - looks like mistletoe)

It only has 43 mentions so far on altavista, most of which have nothing to
do with pharmacology. You can probably get it -now- in chinatown. I hope
it is a better smart drug than ginkgo! It has better stats (If I remember
correctly) than lucidril in its one study of 50 Alzheimers patients...

If someone tries it, and writes about it, their essay will get zillions of
hits (like the 85K to DXM!). GNC (the safeway of pill stores) might start
putting it in tablets in a few months. If you essay on this please do a
rigorous test...

Fig leaf: I'm really not into drugs; I'm just fascinated by improvements
in legal nootropics.

Stuff from medline (
*** next to each title

then a leak re:GNC I read on some link I got from pg 1 altavista:

Effect of huperzine A, a novel acetylcholinesterase
inhibitor, on radial maze performance in rats.

Xiong ZQ, Tang XC

Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy
of Sciences.

Rats were trained to run in a spatial, radial arm maze using a procedure
to determine two memory functions, working and reference memory. The
muscarinic antagonist, not the nicotinic antagonist, impaired both working
and reference memory of rats. Scopolamine (0.125, 0.15, and 0.2 mg/kg, IP,
30 min before a session) significantly impaired choice accuracy in the
eight-arm maze. In contrast, mecamylamine (5, 10, and 15 mg/kg) did not
affect the performance. Huperzine A (0.1, 0.2, and 0.3 mg/kg, IP, 30 min
before testing) and physostigmine (0.3 mg/kg, IP, 20 min before testing)
could reverse scopolamine-induced deficits in the task. Chronic treatment
with huperzine A (0.25 mg/kg, PO, once a day) for 8 consecutive days was
as potent as acute treatment on attenuating the scopolamine-induced

*** Gotta love it - helpful against nerve gas.
Huperzine A as a pretreatment candidate drug against
nerve agent toxicity.

Grunwald J, Raveh L, Doctor BP, Ashani Y

Israel Institute for Biological Research, Ness-Ziona.

Huperzine A (HUP) is a naturally-occurring, potent, reversible inhibitor
of acetylcholinesterase (AChE) that crosses the blood-brain barrier. To
examine its ability to protect against nerve agent poisoning, HUP was
administered i.p. to mice, and the s.c. LD50 of soman was determined at
various time intervals after pretreatment. Results were compared to those
obtained for animals treated with physostigmine. A protective ratio of
approximately 2 was maintained for at least 6 hr after a single injection
of HUP, without the need for any post-challenge drug therapy. By contrast,
pretreatment with physostigmine increased the LD50 of soman by 1.4- to
1.5-fold for only up to 90 min. The long-lasting antidotal efficacy
displayed by HUP correlated with the time course of the blood-AChE
inhibition. The results suggest that the protection of animals by HUP from
soman poisoning was achieved by temporarily sequestering the active site
region of the physiologically important AChE.

Efficacy of tablet huperzine-A on memory, cognition, and
behavior in Alzheimer's disease.

Xu SS, Gao ZX, Weng Z, Du ZM, Xu WA, Yang JS, Zhang ML, Tong ZH, Fang YS, Chai XS,
et al

Zhejiang Supervision and Detection Station of Drug Abuse, Zhejiang Medical
University, Hangzhou,

AIM: To evaluate the efficacy and safety of tablet huperzine-A (Hup) in
patients with Alzheimer's disease. METHODS: Using multicenter,
prospective, double-blind, parallel, placebo controlled and randomized
method, 50 patients were administered orally 0.2 mg (4 tablets) Hup and 53
patients were given po 4 tablets of placebo bid for 8 wk. All patients
were evaluated with Wechsler memory scale, Hasegawa dementia scale,
mini-mental state examination scale, activity of daily living scale,
treatment emergency symptom scale, and measured with BP, HR, ECG, EEG,
ALT, AKP, BUN, Cr, Hb, WBC, and urine routine. RESULTS: About 58% (29/50)
of patients treated with Hup showed improvements in their memory (P <
0.01), cognitive (P < 0.01), and behavioral (P < 0.01 functions. The
efficacy of Hup was better than placebo (36%, 19/53) (P < 0.05). No severe
side effect was found. CONCLUSION: Hup is a promising drug for symptomatic
treatment of Alzheimer's disease.

Huperzine A ameliorates the spatial working memory
impairments induced by AF64A.

Zhi QX, Yi FH, XI CT

Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy
of Sciences,
People's Republic of China.

Huperzine A, a novel, potent, reversible, and selective
acetylcholinesterase (AChE) inhibitor has been expected to be superior to
other AChE inhibitors now for the treatment of memory deficits in patients
with Alzheimer's disease. We have assessed the effects of huperzine A on
performance of AF64A-treated rats in the radial maze. AF64A (2 nmol per
side, i.c.v.) caused significant impairment in rats' ability to perform
the spatial working memory task. This behavioural impairment was
associated with a significant decrease in the activity of choline
acetyltransferase (ChAT) in the hippocampus. Huperzine A (0.4-0.5 mg kg-1,
i.p.) significantly ameliorated the AF64A-induced memory deficit. These
results suggest that AF64A is a useful agent for disrupting working memory
processes by altering hippocampal cholinergic function, and such
impairment can be effectively ameliorated by huperzine A.

***Some fun non huperzine stuff in this one too
Development of natural products as drugs acting on
central nervous system.

Zhu XZ

Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy
of Sciences.

We have recently studied several natural product constituents which have
effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were
isolated from Corydalis ambigua and various species of Stephania. (+)-THP
and (-)-THP possess not only analgesic activity, but also exert
sedative-tranquilizing and hypnotic actions. Results of receptor binding
assay and their pre- and post-synaptic effects on dopaminergic system
indicate that (-)-THP and (-)-stepholidine are dopamine receptor
antagonists while (+)-THP is a selective dopamine depletor. (2)
3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The
relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912
times that of morphine and aspirin, respectively. The analgesic effect of
AAC was not antagonized by naloxone, but was eliminated by reserpine. In
monkeys, after AAC was injected for 92 days, no abstinence syndrome was
seen after sudden AAC withdrawal or when challenged with nalorphine. (3)
Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which
was found to be a selective ChE inhibitor and could improve learning and
retrieval processes. Preliminary clinical studies showed that Hup-A
improve short- and long-term memory in patients of cerebral
arteriosclerosis with memory impairment. (4) Ranamargarin is a new
tetradecapeptide isolated from the skin of the Chinese frog Rana
margaratae. This peptide may mainly act on NK-1 receptor.

***Delta waves! EEG power eeek.
[Effects of huperzine A on electroencephalography power
spectrum in rabbits].

[Article in Chinese]

Guan LC, Chen SS, Lu WH, Tang XC

Huperzine A (Hup-A) is a new alkaloid extracted from Huperzia serata in
China. The effects of Hup-A on learning and memory are superior to those
of physostigmine (Phys). The purpose of this paper is to observe the
effects of Hup-A on EEG and EEG power spectrum in rabbits with
micro-computer analysis. Hup-A 0.1 mg/kg iv in conscious rabbits produced,
after 0.5 min, an alert EEG pattern, which showed decreases of lower
frequency components and the total EEG power in cortical area, and the
dominant frequency transferred from delta rhythm to theta rhythm in
hippocampus. The same effects were seen with Phys 0.1 mg/kg. Scopolamine
(Scop, 0.2 mg/kg iv) reversed significantly these effects of Hup-A (10
micrograms/rabbit, icv), but Scop butylbromide (0.4 mg/kg, iv) which can
not pass the blood-brain barrier did not. Hup-A 0.2 mg/kg iv or Phys 0.3
mg/kg iv antagonized the EEG effects of Scop 0.3 mg/kg iv. The results
indicate that the effects of Hup-A are closely related to the action on
the central cholinergic system.

*****Favorite part*****

coming to a store near you....

General Nutrition Corp. has notified the Food and Drug Administration of
its intent to market a new dietary ingredient, Huperzine A, an alkaloid
compound extracted from the herb Huperzia serrata.

The supplement will contain Huperzine A at a level of 50 micrograms in a
tablet or capsule, with a suggestion to take once per day, the firm said
in an Aug. 25 letter, placed on the public record after the 75-day
premarket notification period required under the Dietary Supplement Health
and Education Act...

Postnote: 50mcg tablets = 1/4 the dose in the alzheimer's study.